Are neoantigens a promising approach in cancer treatment?

Cancer treatment has been evolving throughout the years. New knowledge regarding this disease has been discovered and has been applied to the clinic. For example, surgical techniques, radiotherapy, precision surgeries, chemotherapy, immunotherapy, and CAR T cells therapies. There is also a new trend in research regarding neoantigens and it may seem more promising than everyone thought.

Cancerous cells have a very high mutation burden in their DNA. It is expected, and it does happen, that those mutations translate into proteins, which are called neoantigens. Initially, neoantigens were not considered as potential targets to treat diseases because of the wide variety there exists, due to the great number of mutations present in cancerous cells. However, these neoantigens may be recognized by T cells, providing a different approach in cancer treatment. Using sequencing of cancer genomes, scientists can predict the mutations and neoantigens, facilitating the development of personalized treatments depending on the neoantigens present in the disease. One approach can be a type of personalized cancer vaccine. For those cases, the mutations in the tumor for a specific patient should be identified by sequencing techniques. The vaccine could be designed to target specific neoantigens against cancer. By applying the vaccine, this could activate the immune system and target the cancerous cells.

For example, in one preclinical research model using mice, Castle et al. targeted in mice a mutation of a dominant antigen (K739N) and then immunized the mice with the mutated antigen. Results showed that mice that received the vaccine showed decreased disease progression and improved survival rates. There have also been some clinical trials using cancer vaccines targeting neoantigens. In a study from Ott et al., 6 patients with melanoma were enrolled and their tumor mutations were detected by new generation sequencing. The researchers predicted which neoantigens could be useful by algorithms and they were vaccinated with those personal tumor neoantigens. From this research, they found out that four patients had no recurrence of the disease in a period of 25 months. The other two patients did have recurrence, but were treated then with anti PD-1 therapy and then experienced tumor regression.

There are promising results from research like the ones described above, however, there are several obstacles to overcome regarding the therapies using neoantigens. For example, there are some cancers that don’t respond well to immunotherapy, such as pancreatic cancer. Another thing to consider with these types of treatments is the cost. Since the treatment would be personalized, scaling up the process could not be possible, and costs would increase. Translational research or also known as “bench-to-bedside” may be a very useful approach to accelerate the research being made in this subject. We hope we can be part of this approach in the near future, as in Althian we care about having the newest treatment options for our patients.